Material suitable for an individual&#39;s tissue reconstruction

ABSTRACT

The invention relates to a material suitable for the reconstruction of an individual&#39;s tissue, in particular supportive tissue such as bone tissue, insertable into the tissue. It is characteristic that it is made up of wood heat-treated within the temperature range of 100-220° C. in the presence of water vapor. The invention also relates to the use of the material.

[0001] The invention relates to the material defined in the preamble ofclaim 1 and to the use thereof.

BACKGROUND

[0002] The publications referred to below and used for elucidating thebackground of the invention and the state of the art are to be viewed asbeing incorporated into the description of the invention presentedbelow.

[0003] By “tissue” is meant herein both hard tissue (bone, tooth andcartilage) and soft tissue. A supportive tissue may be a hard tissue orsoft tissue structure, such as a tendon, connective tissue or ligament.

[0004] Materials tested and used for the reconstruction of supportivetissue, in particular bone tissue, include calcium phosphate basedmaterials made, for example, from bovine bone, hydroxyapatite preparedby chemical methods, calcium phosphate, tri-calcium phosphate,coral-based hydroxyapatites, bioactive glasses, metals or metal alloys(e.g. titanium or vitallium), a large group of polymers, and bone tissueitself, either the patient's own bone (autograft) or bank bone(allograft) (Aho & Heikkilä 1997). There are adverse effects associatedwith all of these materials because of the complicated manufacturingprocess of the material, unsatisfactory strength of the material, itscumbersome handling property or its unsatisfactory workability, orpotential risk of contagious disease. There has been a search for amaterial which would not have the above-mentioned adverse effects andwhich would additionally correspond to bone tissue by its structure andresilience and be easily workable. By workability is meant in particularthe shaping of a piece, sawing, carving and drilling of the material,and the attaching of the piece at its targeted site. The workability ofthe known materials mentioned above is unsatisfactory. Furthermore, theyare brittle and prone to break.

[0005] In 1997 there was published in the literature, in the form of anabstract, a report on experimentation with wood, i.e. juniper, in rabbitbone (Gross et al., 1997). The juniper wood used in this experimentationwas, however, in no manner pre-treated.

OBJECT OF THE INVENTION AND SUMMARY OF THE INVENTION

[0006] The object of the present invention is to provide a novelmaterial suitable for the reconstruction of an individual's tissue, inparticular the reconstruction of supportive tissue, such as bone tissue.

[0007] A particular object is to provide a material that allows theformation of new tissue inside the material and/or favors theintegration of tissue with the surface of the said material.

[0008] It is also an object to provide a material that can be combinedwith a bioactive material, various active agents or agents promotingbiodegradability.

[0009] It is also an object to provide a material from which a piecewith good strength properties can be made, the workability of which isgood, and the structure of which, nevertheless, allows the formation ofnew tissue inside the piece and/or integration of tissue with it.

[0010] These objects are achieved with the material according to theinvention, the characteristics of the material being given in theclaims.

[0011] The object of the invention is thus a material suitable for anindividual's tissue reconstruction, in particular the reconstruction ofsupportive tissue, such as bone tissue, insertable into the tissue, thematerial being characterized in that it is made up of wood heat-treatedwithin the temperature range of 100-220° C. in the presence of watervapor.

[0012] The invention also relates to the application of the novelmaterial to various medical or dental, in particular surgical ortherapeutic purposes, i.e. for rectifying various defects of supportivetissue, in particular bone or the skeletal structure; as part of a bone;as articular cartilage surfaces; as filler for bone cavities; for thereconstruction of long bones; as correction plates for the fundus of theeye or facial bones or as a filler material for cavities; as a cranialplate; as a nail; as a screw; as a piece for vertebral repair; as a bonecement component; as a joint prosthesis or an implant either as such orcombined with metal prostheses, metal plates or metal implants; as a jawand/or tooth implant; as a mineralizing toothpick; as an occlusalsplint; as a parodontal filler; as tooth cement; as surgical paste; as atissue-guiding membrane or tube; as a protective fabric; as a wounddressing fabric; in combined use with autogenic or allogenic bone; or asan ingredient in other biomaterial preparations, such as plastics (e.g.acrylics) or various compositions.

PREFERRED EMBODIMENTS AND A DETAILED DESCRIPTION

[0013] The wood used in the present invention may be either hardwood orsoftwood. Usable hardwood species are primarily birch, aspen, oak, alderand poplar, and usable softwood species pine, juniper, spruce and larch.

[0014] Rendering wood usable in a tissue presupposes its sterilization,i.e. the elimination of any bacteria, molds, fungi and spores present init. This is achieved by heat-treating the wood material within thetemperature range of 100-220° C. in the presence of water vapor, wherebythe igniting of the wood is prevented. Heating to a temperature above100° C. changes the physical and chemical properties of wood. Within thetemperature range of 100-200° C., water leaves the wood, and the polymerchains of carbohydrates break and free acids are formed. Thecarbohydrates break down further and the pyrolysis of lignin and woodbegins (Pecina & Paprycki 1988). What is essential is thus the partialbreaking down in various ways of the principal components of wood, i.e.cellulose, hemicellulose and lignin.

[0015] The acetic acid formed in the breaking down of cellulose andhemicellulose de-polymerizes the microfibrils of cellulose. Solublesugars are formed in the hydrolysis of hemicellulose (Hillis 1984).During heat treatment, polysaccharides are also formed by hot and coldextraction (Fengell 1966). The pentosans of hardwood break down morereadily than the hexanes of softwood (Kollman & Fengell 1965), and theeffect of the heat treatment on the wood of different species depends onthe type and amount of the hemicellulose. Lignin withstands heat best.

[0016] The wood material according to the present invention is heattreated with humid air in the presence of water vapor (Viitaniemi &Jämsä 1996). This method is also described in Finnish patent FI 103834.Such a method has also been used in the wood industry for improving thedecay resistance of wood. Owing to the heat treatment the color of thewood darkens, its decay resistance and mold resistance increasestrongly, its moisture expansion decreases by 80-90%, and its bendingstrength decreases by 10-15%. Changes are observable in the fiberstructure of the wood, e.g. longitudinal cracks in the cell walls.

[0017] According to a suitable embodiment, care is taken during the heattreatment that the difference between the internal temperature of thepiece of wood and the temperature of the medium (air and water vapor)surrounding the piece of wood is limited, preferably it is at maximumapprox. 30° C. In this manner it is ensured that cracks weakening thestrength are not formed in the wood material.

[0018] The water vapor used is preferably a saturated water vapor.

[0019] The wood material thus treated can be worked to the desiredshape, allowing also the drilling of holes.

[0020] According to another option it is possible first to work piecesof the desired shape from the wood and to heat-treat the pieces onlythereafter.

[0021] According to a further option, a piece of the desired shape canbe prepared by compressing heat-treated wood particles, such as sawdustor wood powder, or particles elongated in the longitudinal orientationof the wood fibers. In the compression it is possible to use suitableadditives that promote the coherence of the piece, such as acrylicplastics or other tissue adhesives. A piece compressed from woodparticles is suitable for use for purposes wherein strengths are lesscritical properties. From the elongated wood particles mentioned aboveit is possible to compress pieces having a desired resilience, tensilestrength and plasticity. By varying the size and shape of the particlesit is possible to regulate the said properties to a large extent.

[0022] According to a further option, wood particles can be used as such(i.e. without compressing them into a piece), for example, as a fillermaterial for bone cavities.

[0023] The heat treatment of the wood can be carried out while the woodis either in the form of a relatively large piece or in particulateform.

[0024] According to a highly recommended embodiment, a bioactivecomponent is also added to the material according to the invention. Bythe addition of a bioactive component the integration of the woodstructure and the surrounding tissue (bone and/or connective tissue) canbe improved and accelerated. The bioactive component may additionallyhave one or more of the following properties: bonding with tissues ortissue-mineralizing, biocompatible, biodegradable or releasing activeagents (e.g. anti-microbial). The bioactive component may be a bioactiveglass, a bioactive polymer, a silica gel, e.g. xerogel, Ti gel, aceramic material, a glass ceramic material, calcium phosphate,hydroxyapatite, coral, or allogenic or autogenic bone, or any mixture ofthe above-mentioned components (Aho 1993; Heikkilä et al. 1995; Buchholzet al. 1987; LeGeros & LeGeros 1993; Kangasniemi 1993).

[0025] The bioactive component may be present in various forms, such asions, particles, granules, spherules, fibers, rods or films. Thus thebioactive component may be combined with the wood material in differentways.

[0026] The combining of the bioactive component with the wood materialcan be carried out in different ways. If the wood material is in aparticulate form, it can be mixed with a particulate bioactive material.When so desired, the mixture can be compressed into a piece. If the woodmaterial is present in the form of a continuous piece of wood, abioactive material in a finely-divided form may be introduced inside thepiece by means of either a gas or a liquid stream. It is thus possibleto use pressurized precipitation (whereby a fine powder is transportedto the inside of a piece of wood), various mineralization techniques(impregnation with solutions), etc. The bioactive component and thecarrier liquid stream may, for example, be present as a solution, in theform of a colloidal solution such as a sol, suspension or emulsion. Thebioactive component may also be present as a separate layer relative toa piece shaped from a wood material, for example as a coating or alaminate. A combination of all of the above is also possible.

[0027] It is also possible to add to the wood material other substanceshaving physiologically advantageous effects, either as such or togetherwith a bioactive component described above. Such active agents includegrowth factors, proteins (e.g. bone morphogenetic protein, BMP), drugs(e.g. antibiotics or cytostatic drugs), sugars, hormones (such ashormones having anabolic action), enzymes, other organic substances,such as collagen, hyaluronic acid and antioxidants. Furthermore, it ispossible to treat the wood material by using genetic engineering, e.g.by transferring into it a growth-increasing gene (e.g. a virus gene).The type of the additive used is determined by the targeted use onmedical grounds, the purpose being to improve and to speed up tissuegrowth and to affect the basic disease, such as cancerous tissue and/orinflammation.

[0028] It is also possible to combine with the wood material a plasticscomponent as a paste, in a soluble form or in a thermoplastic form (e.g.lactide/caprolactone), with which the splintery structure of wood isimpregnated by the methods described above.

[0029] If it is desired to promote and accelerate the biodegradabilityof the wood material, also such agents can be added to it. By a specialchemical technique this wood material can be treated so that it iscaused to degrade in a controlled manner, in which case it may beentirely replaced with the parent tissue, e.g. bone. Further examples ofsubstances of this type are enzymes, such as collagenases and proteases,catepsin, and streptokinase or streptodomase, or gene transfer methods.

[0030] The wood material may form a dense or in different degrees porouspiece, e.g. a prosthesis. It may be shaped, according to its targeteduse, as a rod, plate, membrane or sphere, or to correspond to therequired anatomic structure.

[0031] It is also possible to manufacture coatings and membranes fromthe wood material. The wood material may be netlike, filamentous, or inparticle form, such as a fiber, powder or granular sawdust, or a shapedpiece, such as a plate, tube, rod, nail or screw. The purpose is to useit for the correction of an anatomic structure, but also for attachingit or a bone by means of a wooden nail or other such spike via a bore.The structure according to the invention may also in its piece-like formcontain holes or conduits corresponding to the osteonic structure of theshell layer of the bone, and its macrostructure may be tubular, i.e.hollow, corresponding to, for example, the core and overall structure ofa long bone. It may be a lamellar plate structure, smooth or modified.The product may be soft, resilient, brittle or hard mineralized.

[0032] A material to be fitted in connection with body tissue must, ofcourse, be sterile. In consequence of the heat treatment the microbespresent in the wood die, but nevertheless a final sterilization of theproduct, for example by means of heat or irradiation, is recommended.

[0033] Uses of the material according to the invention that can bementioned include, in supportive tissue structures, bone and cartilagedefects. Practical targeted uses include filler material for bonecavities, reconstruction of long bones or flat bones with a platefastener, core nail or screw, correction plate for the fundus of theeye/facial bones, cranial plate, vertebral repair plate, bone cementcomponent, joint prosthesis, or implant coating for metal prostheses orplates. Applications in the teeth and the jaws include dental implantcoating, jawbone implant, occlusal splint, paradontal filler,mineralizing toothpick, paste or dental segment, or surgical paste.Other applications include tissue guiding membrane or tube, cell tissuegrowing net, frame, protective fabric, wound dressing fabric, joint usewith autogenic or allogenic bone, and carrier substance for activeagents such as drugs.

[0034] The purpose is to use the material according to the inventionspecifically in the following conditions:

[0035] 1) Defects arising in connection with bone tumors or re-surgeryof hip or knee prostheses; these are defects which are eithercavity-like or comprise the cartilage-bone part of the bone epiphysisand the joint, or a segment of the diaphysis or the longitudinalhemisphere of a long bone (cf. FIGS. 1, 2 and 3).

[0036] 2) Bone defects arising in connection with various fractures in along bone, flat bones or vertebrae, which would require a bonetransplant as a treatment.

[0037] 3) An joint (hip, knee) prosthesis of a novel type may be madefrom the material according to the invention (cf. FIG. 4).

[0038] 4) Developmental and late impairment of the bones and othersupportive tissues, also comprising conditions within the scope ofdentistry in the jawbones and joints and in teeth, such as congenitaldevelopmental anomalies and defects and bone deficiencies developinglater in life, for example, those caused by infections, osteoporosis andosteopenia.

[0039] 5) In dentistry the attachment of implants and dentures, growingand shaping of the bone ridge, toothpicks (mineralizing).

[0040] 6) A combination of wood cells and bone cells may replace the useof autograft or allograft, i.e. bank bone.

[0041] Bone defects arising from cancer surgery can be mentioned as avery concrete targeted use. A malignant or aggressive bone tumor in along bone may have to be treated by removing a portion of the said longbone surgically, whereby an extensive, for example 10-15 cm long, areawhere bone is absent is formed. This absent bone can be replaced with awood piece of the corresponding shape and size (possibly also containingother components, such as a bioactive component and an active agent),which is inserted into the area (e.g. hip bone or leg bone). The pieceis attached either with a surgical plate with screws or best with a corenail. In this case the function of the bone and the joint is retainedand it is possible for bone tissue to integrate with the said implant(cf. FIGS. 1-4).

[0042] The behavior of the material according to the invention in boneis described in greater detail with the help of the following example.

EXAMPLE

[0043] In the studies conducted, conical or cylindrical (2.5×5 mm)implants made from heat-treated wood (aspen, birch, pine) were insertedinto bores in the cancellous bone of a rabbit's knee. A microscopicexamination of the implant cavities at 4-8 weeks showed that in severalareas the wood fiber structure was in direct tissue contact with thebone. The connective tissue formed on the edges of the cavities wasstructurally closely integrated with it. In the interface, macrophageswere seen, but no round cells or lymphocytes, i.e. no actual immunogenicreaction was detected. The macroscopically small pieces of wood wereclean on the surface of the bone and cartilage, without accumulation offluid. At twenty weeks the bone was more abundantly attached to thematerial, and small islands of bone and osteoid tissue were seen in itscanalicular inner structure.

[0044] Heat-treated wood enables living bone to integrate with the woodfiber structure. This phenomenon is promoted by the partial micro- andmacroscopic similarity of the structures of wood and compact bonetissue. There is namely observable in wood a system of wood cellslocated cylindrically one inside the other, the cells beinginterconnected by passages running in both the longitudinal and thelateral orientations. In compact bone, e.g. in the cortical bone of along bone, there are also cylindrical, lamellar tubular, sheet-likestructures formed by hydroxyapatite-collagen strands and located oneinside another. Blood vessels are located in the center of these,connecting them also in the transverse direction. A bioactive component,e.g. bioactive glass, promotes and further accelerates the integrationof the bone tissue with the implant structurally and chemically.

[0045] The embodiments cited above are only examples of theimplementation of the idea of the invention. For a person skilled in theart it is clear that the various embodiments of the invention may varywithin the scope of the claims presented below.

[0046] Literature References

[0047] Aho A J, Heikkilä J T. Bone substitutes and related materials inclinical orthopaedics. In: Advances in Tissue Banking, Vol. 1, eds.Phillips G 0, Versen R, Strong M, Nather A. World Scientific, Singapore1997:73-107.

[0048] Aho A J, Heikkilä J T, Andesson Ö H, Yli-Urpo A. Morphology ofosteogenesis in bioactive glass interface. Ann Chirurg Gynaecol1993;82:145-153.

[0049] Bucholz R W, Carlton A, Holmes R. Hydroxyapatite and tricalciumphosphate as bone graft substitutes. Orthop Clin North Am1987;18:323-334.

[0050] Fengell D. Heiss- und Kaltwasserextrakte von thermischbehandeltem Fichtenholz. Holz Roh Werkst 1966;24:9-14.

[0051] Gross, Ezerietis E, Gardovskis J, Skudra M, Vetra J. Juniperwoods as an alternative implant material. 13th Conference ofBiomaterials. Göteborg, Sweden Sep. 4-7, 1997. P. 36.

[0052] Heikkilä J. Bioactive glass as a bone substitute in experimentaland clinical bone defects. Thesis. Ann Univ Turkuensis Ser D Tom 240.Turku 1996.

[0053] Heikkilä J T, Aho A J, Aho H J, Yli-Urpo A, Happonen R-P. Boneformation in rabbit cancellous bone defects filled with bioactive glassgranules. Acta Orthop Scand 1995;66:463-467.

[0054] Hillis W. High temperature and chemical effects on woodstability. Part 1: General considerations. Wood Sci Technol1984;18:281-293.

[0055] Kangasniemi I M 0. Development of Ca, P-ceramic containingbioactive glass composites. Thesis. University of Leiden, TheNetherlands 1993.

[0056] Kollman F, Fengell D. Änderungen der chemischen Zusammensetzungvon Holz durch thermische Behandlung. Holz Roh Werkst 1965;23:461-468.

[0057] LeGeros R Z, LeGeros J P. Dense hydroxyapatite. In: Anintroduction to bioceramics, eds. Hench L L, Wilson J, World Scientific,Singapore 1993:139-180.

[0058] Pecina H, Paprzycki 0. Wechselbeziehungen zwishen derTemperaturbehandlung des Holzes und seiner Benetzbarkeit. HolzforschHolzverwert 1988;40:5-8.

[0059] Roffael E, Schaller K. Einfluss thermischer behandlung aufCellulose. Holz Roh Werkst 1971;29:275-278.

[0060] Viitaniemi P, Jämsä S. Puun modifiointi lämpökäsittelyllä. VTTPublications 814. Espoo 1996.

1. A material suitable for the reconstruction of an individual's tissue,in particular supportive tissue, such as bone tissue, insertable intothe tissue, characterized in that it is made up of wood heat-treatedwithin the temperature range of 100-220° C. in the presence of watervapor.
 2. The material according to claim 1, characterized in that thewood is treated so that the difference between the internal temperatureof the wood and the medium surrounding the wood is limited, preferablyto at maximum approx. 30° C., and that the water vapor is a saturatedwater vapor.
 3. The material according to claim 1 or 2, characterized inthat it is a piece shaped from wood, such as a plate or a rod, theshaping having been carried out before the heat treatment of the wood orafter it.
 4. The material according to claim 1 or 2, characterized inthat it has been shaped into the desired piece by compressing togetherwood particles, such as wood sawdust or wood powder, or particleselongated in the longitudinal orientation of the wood fibers.
 5. Thematerial according to any of claims 1-4, characterized in that itadditionally comprises a bioactive component.
 6. The material accordingto claim 5, characterized in that the bioactive component, which is in afinely-divided form, is introduced into a whole piece of wood by meansof a liquid or gas stream.
 7. The material according to claim 5,characterized in that the bioactive component, which is present in aparticulate form, is mixed with wood material in a particulate form,whereafter the mixture is compressed into the desired piece.
 8. Thematerial according to claim 5, 6 or 7, characterized in that the saidmaterial is shaped into a piece and that the bioactive component ispresent as a layer separate relative to the piece, for example, as acoating or a laminate.
 9. The material according to any of claims 5-8,characterized in that the bioactive component is a bioactive glass, abioactive polymer, silica gel, Ti gel, a ceramic material, a glassceramic material, calcium phosphate, hydroxyapatite, coral, or allogenicor autogenic bone, or any mixture of the above-mentioned components. 10.The material according to any of the preceding claims, characterized inthat it contains an active agent, such as a drug, e.g. an antibiotic ora cytostatic drug; a growth factor; a protein; a sugar; a hormone; anenzyme; a collagen or an antioxidant; or a substance degrading thematerial in a controlled manner; or any mixture of the above-mentionedsubstances.
 11. The material according to any of claims 1-10,characterized in that it comprises a substance promoting thebiodegradability of the said material.
 12. Use of the material accordingto any of claims 1-11, characterized in that it is used for the repairof various defects of a supportive tissue, in particular bone or theskeletal system; as part of a bone; as joint cartilage surfaces; as afiller material for bone cavities; for the reconstruction of long bones;as a correction plate of the fundus of the eye or facial bones or afiller material of cavities; as a cranial plate; as a nail; as a screw;as a repair piece of a vertebra; as a bone cement component; as a jointprosthesis or implant as such or combined with metal joint prostheses,plates or implants; as a jawbone and/or tooth implant; as a mineralizingtoothpick; as an occlusal splint; as a parodontal filler material; as atooth cement; as a surgical paste; as a tissue-guiding membrane or tube;as a protective fabric; as a wound dressing fabric; in combined use withautogenic or allogenic bone; or as an ingredient in other biomaterialpreparations, such as plastics (e.g. acrylics) or various compositions.